Even though the National Kidney Foundation guidelines recommend a dietary protein intake >1.2 g/kg/d in hemodialysis (HD) patients, it remains unclear whether high protein intake has beneficial or harmful nutritional and cardiovascular (CV) effects in this population. Our earlier data suggest that high protein intake might improve nutritional status but it has been argued that the state of low muscle mass, small body size and low serum protein levels is not the result of decreased dietary intake, rather hypercatabolism induced by metabolic acidosis, inflammation and oxidative stress. Therefore, a high protein intake in HD patients might be harmful by worsening metabolic acidosis without improving nutritional status. The effects of protein intake on cardiovascular disease are also controversial. Malnutrition has been considered to be a uremic CV risk factor. On the other hand, it also been suggested that high protein intake might t serum phosphorus and arterial calcification with the attendant consequences of arterial stiffness and myocardial stress. The relative risks and benefits of high dietary protein intake in HD patients are therefore unresolved. We hypothesize that in the HD population overall: (1) Protein intake is a major determinant of muscle mass while inflammation, oxidative stress and metabolic acidosis play a lesser role; (2) Malnutrition is not an uremic CV risk factor hence low protein intake does not cause CV disease; and (3) In the other extreme, high protein intake is also not a major cause of CV disease since high serum phosphorus associated with high protein intake can usually be controlled by the use of phosphorus binders in routine clinical practice. The specific aims of this revised application are to examine in HD patients, the longitudinal associations of absolute total protein intake (TPI in g/day) or dietary protein intake normalized to body weight (DPI in g/kg/day) with 1. Nutritional status (mid-thigh muscle mass as measured by MRI) and functional status (6- minute walk) and 2. Arterial stiffness (aortic pulse wave velocity) and myocardial injury (serum cardiac troponin T). The study population will be a prospective cohort of 210 HD patients recruited at Utah and Northern California. Protein intake is measured by dietary records and urea kinetic modeling. Protein intake, 6- minute walk, aortic pulse wave velocity and serum cardiac troponin T will be measured at baseline, 6, 12, 18 and 24 months, Mid-thigh muscle mass will be measured at baseline, 12 and 24 months. The longitudinal associations of protein intake with mid-thigh muscle mass, 6- minute walk, aortic pulse wave velocity and serum cardiac troponin T will be examined in multivariate mixed effects models. The study has adequate power to test the proposed end-points. Relevance to public health: This study will examine in HD patients the role of protein intake in malnutrition and cardiovascular disease, two of the most important problems in these patients. [unreadable] [unreadable] [unreadable] [unreadable]